The proposed research continues to have as its major aim the establishment of chromosome changes in bladder cancer and correlation of the findings with various histologic, clinical, biologic and prognostic parameters of the disease. Recent establishment in our laboratory of specific (primary) chromosome changes in bladder cancer appears to indicate that several subgroups may exist within this disease entity. To-date, three karyotypically defined subgroups have been established in terms of the primary karyotypic changes. The latter consist of an isochromosome for the short arm of chromosome #5, i(5p), trisomy for chromosome 7 and 9q/-9. Since a strong possibility exists that the primary changes are related to etiology, it would appear that these three subgroups of bladder cancer may have different backgrounds in their genesis. The future research will address itself towards correlating the primary chromosome changes with such parameters as stage and grade of the bladder cancer, geographic location within the bladder, invasiveness, metastatic spread, recurrence and prognostic and survival parameters. In addition to the primary changes, the secondary chromosome changes, which may play a crucial role in the biology of the cancer, particularly its progression and resistance to therapy, will also be ascertained and correlations of a similar nature as mentioned above made with these changes. Thus, in the forthcoming years we hope to define bladder cancer in terms of the cytogenetic findings, both primary and secondary, and establish at least cytogenetically defined subentities within the disease akin to the cytogenetic classification of the leukemias. In addition, various molecular probes will be used, the exact type depending on the primary and secondary chromosome changes in the tumor. The parameters to be investigated include specific oncogene and other gene expressions in bladder cancers, in order to evaluate the role that the primary and secondary karyotypic changes may play in the initiation and expression of genic material.